Wang Luojia, Wang Zhongzhong, Luo Wang, Zhao Heping, Xie Guoming
Key Laboratory of Clinical Laboratory Diagnostics (Chinese Ministry of Education), College of Laboratory Medicine, Chongqing Medical Laboratory Microfluidics and SPRi Engineering Research Center, Chongqing Medical University, Chongqing 400016, PR China.
Honghui Hospital, Xi'an Jiaotong University, Xi'an 710054, PR China.
ACS Appl Bio Mater. 2024 Dec 16;7(12):8599-8607. doi: 10.1021/acsabm.4c01366. Epub 2024 Dec 4.
Living systems have some of the most sophisticated reaction circuits in the world, realizing many incredibly complex functions through a variety of simple molecular reactions, in which the most notable feature that distinguishes them from artificial molecular reaction networks is the precise control of reaction times and programmable expression. Here, we exploit the hydrolysis-directed nature of λ exonuclease and the programmed responses of the dynamic nanotechnology of nucleic acids to construct a simple, complete, and powerful set of temporally programmed circuits. This system can arbitrarily regulate the degradation rate of the blocker, thereby delaying the nucleic acid chain substitution reaction with less signal leakage. In addition, the powerful dynamic reaction network of nucleic acids enabled us to control the programmed execution of a wide range of reactions in different fields. We have developed a simple strategy to introduce precise control of the time dimension into nucleic acid reaction circuits, which greatly enriches the functionality and applicability of the reaction programs, which can be easily used as timers, compilers, converters, etc. The simplicity, precision, stability, and versatility of such dynamic temporal programming circuits greatly expand the potential of artificial molecular reaction networks for more complex practical applications in biochemistry and molecular biology.
生命系统拥有世界上一些最复杂的反应回路,通过各种简单的分子反应实现许多极其复杂的功能,其中将它们与人工分子反应网络区分开来的最显著特征是对反应时间的精确控制和可编程表达。在此,我们利用λ核酸外切酶的水解导向特性以及核酸动态纳米技术的可编程响应,构建了一套简单、完整且强大的时间编程回路。该系统可以任意调节阻断剂的降解速率,从而以较少的信号泄漏延迟核酸链置换反应。此外,强大的核酸动态反应网络使我们能够控制不同领域中广泛反应的程序执行。我们开发了一种简单策略,将时间维度的精确控制引入核酸反应回路,这极大地丰富了反应程序的功能和适用性,其可轻松用作定时器、编译器、转换器等。这种动态时间编程回路的简单性、精确性、稳定性和通用性极大地扩展了人工分子反应网络在生物化学和分子生物学中更复杂实际应用的潜力。